Inhaled Nitric Oxide in Fibrotic Lung Disease: A Randomized, Double-Blind, Placebo-controlled Trial.

Inhaled nitric oxide (iNO) has been shown to result in benefits in moderate to vigorous physical activity (MVPA) in patients with fibrotic interstitial lung disease (f-ILD) receiving supplemental oxygen in two independent trials. This phase III randomized, double-blind, placebo-controlled study sought to validate the benefit of ambulatory iNO in patients with f-ILD requiring supplemental oxygen. Patients with f-ILD receiving supplemental long-term oxygen were randomized in a 1:1 fashion to iNO at 45 μg/kg ideal body weight per hour or placebo for 16 weeks.

Association of musculoskeletal involvement with lung function and mortality in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with high mortality. Low muscle mass, frailty and sarcopenia lead to functional impairment that negatively impact quality of life and survival but are not used in clinical practice. We aimed to determine the association of Fat-free mass index (FFMI) and frailty with lung function, exercise tolerance and survival in patients with IPF.

Canine acquired pneumonia caused by .

Here, we present the case of a 55-year-old male with HIV and persistent lymphopenia who developed a paroxysmal severe cough for over three weeks. Microbiology studies were positive for abundant colonies of . He reports that his dog was also ill with a severe cough, suggesting a possible canine-to-human transmission.

Lung function trajectories in patients with idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of patients with IPF.

Methods: Patients with IPF that was diagnosed or confirmed at the enrolling centre in the previous 6 months were enrolled into the IPF-PRO Registry between June 2014 and October 2018.

Integrative multi-omics analysis reveals novel idiopathic pulmonary fibrosis endotypes associated with disease progression.

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of extracellular matrix in the pulmonary interstitium and progressive functional decline. We hypothesized that integration of multi-omics data would identify clinically meaningful molecular endotypes of IPF.

Methods: The IPF-PRO Registry is a prospective registry of patients with IPF.

Evaluating the consistency with guideline recommendations for diagnosis and management of idiopathic pulmonary fibrosis in non-academic settings.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with elevated mortality. Delay in diagnosis lead to worse outcomes. Guidelines developed at academic medical centers are difficult to replicate in the community.

Correlates of survival after autoantibody reduction therapy for acute IPF exacerbations.

Background: No medical treatment has proven efficacy for acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF), and this syndrome has a very high mortality. Based on data indicating humoral autoimmune processes are involved in IPF pathogenesis, we treated AE-IPF patients with an autoantibody reduction regimen of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin. This study aimed to identify clinical and autoantibody determinants associated with survival after autoantibody reduction in AE-IPF.

Updated Evaluation of the Safety, Efficacy and Tolerability of Pirfenidone in the Treatment of Idiopathic Pulmonary Fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrotic disease characterized by a progressive decline in lung function with a median survival of 3-5 years after diagnosis. The course of disease is highly variable and unpredictable, often punctuated by episodes of acute respiratory failure, known as acute exacerbations. The incidence of IPF is on the rise due to the aging population, as age is the most important risk factor for this disease.

The senescence-associated matricellular protein CCN1 in plasma of human subjects with idiopathic pulmonary fibrosis.

Introduction: Cellular senescence has been linked to the pathogenesis of idiopathic pulmonary fibrosis (IPF). CCN1 is a matricellular protein that has been shown to induce cellular senescence and contribute to lung fibrosis in pre-clinical models. In this report, we determined plasma CCN1 levels in patients with IPF and its potential role in clinical outcomes.

Decrements of body mass index are associated with poor outcomes of idiopathic pulmonary fibrosis patients.

Background: The processes that result in progression of idiopathic pulmonary fibrosis (IPF) remain enigmatic. Moreover, the course of this disease can be highly variable and difficult to accurately predict. We hypothesized analyses of body mass index (BMI), a simple, routine clinical measure, may also have prognostic value in these patients, and might provide mechanistic insights.

Predicting Outcome in Idiopathic Pulmonary Fibrosis: Addition of Fibrotic Score at Thin-Section CT of the Chest to Gender, Age, and Physiology Score Improves the Prediction Model.

Purpose: To assess the impact of adding thin-section CT-derived semiquantitative fibrotic score to gender, age, and physiology (GAP) model for predicting survival in idiopathic pulmonary fibrosis (IPF).

Materials And Methods: In this retrospective study of 194 patients with IPF, primary outcome was transplant-free survival. Two thoracic radiologists visually estimated the percentage of reticulation and honeycombing at baseline thin-section CT, which were added to give fibrotic score.

Resequencing Study Confirms That Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis.

Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. We performed deep targeted resequencing (3.

Serpine 1 induces alveolar type II cell senescence through activating p53-p21-Rb pathway in fibrotic lung disease.

Senescence of alveolar type 2 (ATII) cells, progenitors of the alveolar epithelium, is implicated in the pathogeneses of idiopathic pulmonary fibrosis (IPF), an aging-related progressive fatal lung disorder with unknown etiology. The mechanism underlying ATII cell senescence in fibrotic lung diseases, however, remains poorly understood. In this study, we report that ATII cells in IPF lungs express higher levels of serpine 1, also known as plasminogen activator inhibitor 1 (PAI-1), and cell senescence markers p21 and p16, compared to ATII cells in control lungs.

Focal adhesion kinase signaling determines the fate of lung epithelial cells in response to TGF-β.

Alveolar epithelial cell (AEC) injury and apoptosis are prominent pathological features of idiopathic pulmonary fibrosis (IPF). There is evidence of AEC plasticity in lung injury repair response and in IPF. In this report, we explore the role of focal adhesion kinase (FAK) signaling in determining the fate of lung epithelial cells in response to transforming growth factor-β1 (TGF-β1).

3D pulmospheres serve as a personalized and predictive multicellular model for assessment of antifibrotic drugs.

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive fibrotic lung disease characterized by the presence of invasive myofibroblasts in the lung. Currently, there are only two FDA-approved drugs (pirfenidone and nintedanib) for the treatment of IPF. There are no defined criteria to guide specific drug therapy.

Alveolar epithelial disintegrity in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive decline in lung function, resulting in significant morbidity and mortality. Current concepts of the pathogenesis of IPF primarily center on dysregulated epithelial cell repair and altered epithelial-mesenchymal communication and extracellular matrix deposition following chronic exposure to cigarette smoke or environmental toxins. In recent years, increasing attention has been directed toward the role of the intercellular junctional complex in determining the specific properties of epithelia in pulmonary diseases.

A bundled care approach to patients with idiopathic pulmonary fibrosis improves transplant-free survival.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with poor prognosis and limited therapeutic options. The 2011 ATS/ERS/JRS/ALAT consensus statement provided a number of recommendations for the management of IPF patients. The primary objective of this study was to determine if "bundling" these recommendations in the management of patients with IPF impacts clinical outcomes.

Targeted Therapy for Idiopathic Pulmonary Fibrosis: Where To Now?

Idiopathic pulmonary fibrosis (IPF) is an aging-associated, recalcitrant lung disease with historically limited therapeutic options. The recent approval of two drugs, pirfenidone and nintedanib, by the US Food and Drug Administration in 2014 has heralded a new era in its management. Both drugs have demonstrated efficacy in phase III clinical trials by retarding the rate of progression of IPF; neither drug appears to be able to completely arrest disease progression.

Systemic sclerosis-associated fibrosis: an accelerated aging phenotype?

Purpose Of Review: Systemic sclerosis (SSc) is an autoimmune disease with fibrosis seen in multiple organs. Although not traditionally regarded as a disease of aging, SSc-associated fibrosis shares many of the hallmarks of aging seen in other age-related fibrotic disorders. Here, we review the current literature of the potential role of aging and age-related cellular processes in the development of SSc and fibrosis.

Therapeutic targeting of SRC kinase in myofibroblast differentiation and pulmonary fibrosis.

Myofibroblasts are effector cells in fibrotic disorders that synthesize and remodel the extracellular matrix (ECM). This study investigated the role of the Src kinase pathway in myofibroblast activation in vitro and fibrogenesis in vivo. The profibrotic cytokine, transforming growth factor β1 (TGF-β1), induced rapid activation of Src kinase, which led to myofibroblast differentiation of human lung fibroblasts.

NADPH oxidases in lung health and disease.

Significance: The evolution of the lungs and circulatory systems in vertebrates ensured the availability of molecular oxygen (O2; dioxygen) for aerobic cellular metabolism of internal organs in large animals. O2 serves as the physiologic terminal acceptor of mitochondrial electron transfer and of the NADPH oxidase (Nox) family of oxidoreductases to generate primarily water and reactive oxygen species (ROS), respectively.

Recent Advances: The purposeful generation of ROS by Nox family enzymes suggests important roles in normal physiology and adaptation, most notably in host defense against invading pathogens and in cellular signaling.